Glutamine: the emperor or his clothes?

1Laboratory of Human Nutrition, School of Science and Clinical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

In this introduction to the Proceedings of the Symposium on Glutamine, we consider various lines of evidence that might potentially lead to an answer to the question posed in the title. We begin with a short summary of the multiple functions of glutamine, which are extensive and, superficially at least, equally as impressive as those of glutamate. However, each of these amino acids may serve an equivalent role in some of these functions due to their ready metabolic interconversion. We raise the question whether glutamine is of primordial or rudimentary significance or whether it is a product of somebody else's existence. Thus, there is a short account of the prebiotic events of evolution that led to the appearance of glutamine and life on Earth. In doing this, it then appears that glutamine is a rather schizophrenic molecule, stable and thermodynamically reliable in biochemical environments, but labile in chemical ones. We then turn to the involvement of glutamine in mammalian N (nitrogen) commerce, with initial emphasis on the nitrogen cycle on Earth, then N transport and N excretion, before assessing its contribution to carbon/energy or C/E commerce. We hypothesize that, in addition to its utilization in immune cell function and in normal intestinal tissues, glutamine is a particularly key anapleurotic and energy-yielding substrate in conditions of hypoxia, anoxia and dysoxia. It also serves as a quantitatively important gluconeogenic metabolite under normal postabsorptive conditions. We postulate that in certain conditions, this carbon-energy econometric function might be by-passed with ornithine. In conclusion, the answer to the question above depends on the context, and this point will receive elaboration in many of the individual contributions that collaborate to form these Proceedings.